In the Laboratory

Using a Premade Grignard Reagent W

To Synthesize Tertiary Alcohols
in a Convenient Investigative
Organic Laboratory Experiment
Michael A. G. Berg*
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060-0212; *bergm@vt.edu

Roy D. Pointer†
Department of Chemistry, Bloomsburg University, Bloomsburg, PA 17815
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This Journal has published a number of interesting labo- Experimental Procedure

ratory experiments utilizing Grignard reagents (1–7). The
importance of utilizing the Grignard reagent is often over- The following is a representative procedure that is gen-
shadowed by the preparation of the Grignard reagent itself. erally followed by the students based on the literature pro-
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Often, the preparation of the Grignard reagent fails (8–12).
Anecdotally, most chemists remember making the Grignard
reagent in second-year organic chemistry, but do not remem-
ber what they used it for. We have felt that while making the
Grignard reagent leaves a lasting impression on our students’
minds, the application of the Grignard reagent is of more
importance. To this aim, we wished to have a laboratory ex-
perience that focused on the carbon–carbon bond formation
aspect of the Grignard reaction by using a commercially avail-
able, premade Grignard reagent. We further wished to make
it an experiment that could easily be performed early in the
second semester of organic chemistry, corresponding to when
the Grignard reaction material is covered in the lecture por-
tion of the course.
Experimental Overview
In our laboratory courses, we wished to foster a degree
of ownership and independent thinking in the laboratory. In
this lab we allow the students to choose which tertiary alcohols
they wish to make, design the workup of the reaction, and
to characterize their product. The students are given a packet
of information on how to perform a Grignard reaction, in-
cluding literature procedures for the synthesis of triphenyl-
methanol (see the Supplemental MaterialW). They are told
to run the Grignard reaction on a scale of 10 millimoles in
which the ketone is the limiting reagent with phenyl magne-
sium bromide used in 10% excess. The students set up their
notebooks with the necessary calculations and physical-con-
stant data. The students assemble the necessary glassware, and
the calculated quantity of phenyl magnesium bromide solu-
tion is dispensed by the instructor. Next, the students slowly
add an ether solution of their ketone and then proceed
through the rest of the reaction, isolation, and purification
steps. They characterize the compound using spectroscopy.
This laboratory can be accomplished in two three- or four-
hour laboratory periods.
†
Retired as an Emeritus Professor from Bloomsburg University.
vided. The students may wish to develop and suggest a
modified procedure for approval by the instructor. However,
the instructor should well understand the Grignard reaction
and handling of air-sensitive reagents and be able to provide
helpful guidance when necessary. We have successfully per-
formed this experiment using other ketones, aldehydes, and
esters, based on student’s interest in trying alternative carbo-
nyl-containing compounds.
A predried three-neck 100-mL round-bottom flask is fit-
ted with a rubber septum, condenser, and an addition fun-
nel. The calculated quantity of the ketone (10 mmol) is
dissolved in 30 mL of anhydrous ether and quickly added to
the addition funnel. The top openings of the condenser and
addition funnel are quickly fitted with plugs of cotton. The
calculated quantity of phenyl magnesium bromide is dis-
pensed from a syringe by the instructor through the rubber
septum into the flask. The ketone solution is slowly added
to the Grignard reagent with stirring. After the initial reac-
tion is complete, the product alkoxide is protonated using
an aqueous acid. The suspension is extracted with several
portions of ether. Residual acid in the combined ether layers
is neutralized by washing with saturated sodium bicarbonate
solution.
The combined ether layers are dried using an anhydrous
drying agent and the ether is evaporated. The solid product
is recrystallized and dried. The melting point and TLC of
the crude and purified alcohol product are compared. Crude
and purified percent yields are calculated and the IR, pro-
ton, and carbon NMR spectra are obtained to characterize
the product.
Hazards
Ether is extremely flammable and should be kept away
from ignition sources such as hotplates and drying ovens!
Ether is also extremely volatile and should be used in a well-
ventilated area. The handling of phenylmagnesium bromide
is discussed below. Care should be taken in preparing aque-
ous sulfuric acid and ammonium chloride solutions.

www.JCE.DivCHED.org • Vol. 84 No. 3 March 2007 • Journal of Chemical Education 483

 In the Laboratory

Table 1. Ketones Used, Average Yields, and Physical Data of the Tertiar y Alcohol Products
Average Melting Point/ CO Stretch/
Ketone Product
Yield(%) ºC cm᎑1c
Benzophenone Triphenylmethanol 54 160–163a 1156
Acetophenone 1,1-Diphenylethanol 65 77–81 a
1192
4-Chlorobenzophenone (4-Chlorophenyl)diphenylmethanol 54 84–85b 1154
a
Ref 13. bRef 14. c
Experimentally derived.

Discussion
Solutions of phenylmagnesium bromide in ether are
readily available from chemical supply companies. These so-
lutions come in bottles fitted with septa-sealed caps. The so-
lution must be transferred from the reagent bottle to the
reaction flask using a clean, dry syringe. Also, all glassware and
Teflon-coated stir bars were kept in a drying oven until ready
for use. In our lab, we had a small, under-the-counter oven,
but were able to easily accommodate twenty setups for the lab.
Additionally, after the equipment was assembled, no extraor-
dinary measures were taken to keep the glassware dry other
than placing a ball of cotton in the top openings of the con-
denser and the addition funnel. For a 14兾20 size joint open-
ing, approximately a 1-cm diameter ball of cotton was used.
The students charged their addition funnel with the ketone
of their choice dissolved in anhydrous ether. The instructor
dispensed the phenyl magnesium bromide into each reaction
vessel using a 10-mL glass syringe with an 18- or 20-gauge 6-
to 10-in. LuerLock needle. The syringe was purged with dry
nitrogen using a simple manifold (see the Supplemental
MaterialW) before the uptake of Grignard reagent solution. The
syringe could be used multiple times before becoming con-
taminated with salt deposits. When this occurred, the syringe
was opened and flushed with ethanol followed by water. (Cau-
tion: This syringe should be set aside and thoroughly dried in
an oven before using again.) We routinely used two or three
separate clean, dry syringes per group of 18 students.
In our lab, students were allowed to select from a choice
of ketones as shown in Table 1. All of the reactions produced
solids. We have allowed students to use other ketones, most
notably, 4-methylbenzophenone and 4-methylacetophenone,
but were unable to isolate solid products from these reactions.
We have also allowed students to use benzaldehyde and sub-
stituted benzaldehydes. However, since these aldehydes oxi-
dize upon storage, the students got significantly lower yields
for the Grignard reaction and a considerable quantity of
byproduct when using old aldehydes. We are also aware that
other premade Grignard reagents are available, such as 4-
chlorophenylmagnesium bromide in diethyl ether and are
currently exploring this reagent as a simple modification for
additional projects.
Summary
We have used this experiment to successfully introduce
students to modern organic synthesis as well as methods in-
volving air-sensitive reagents. The use of the premade Grig-
nard reagent is relatively easy and involves a minimal quantity
of expensive glassware and no inert atmosphere lines other than
a purge for the transfer syringe. In all cases, students are able
to obtain their product in good yields without any of the typical
failures associated with making the Grignard reagent.
W
Supplemental Material
Detailed student instructions for the experiment and
instructor’s notes are available in this issue of JCE Online.
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484 Journal of Chemical Education • Vol. 84 No. 3 March 2007 • www.JCE.DivCHED.org